Hand Foot Mouth Disease During the SARS-CoV-2 Pandemic: A Multicentric Study

Objectives: This prospective observational study aimed to identify the current trend of the circulating viral strains responsible for hand foot mouth disease (HFMD) outbreak in four tertiary care centers in Rajasthan, amidst the coronavirus disease (COVID-19) pandemic (April-October 2022). Methods: Cases with suspected HFMD, presenting to our skin outpatient department were assessed clinically and serologically (IgM antibodies against coxsackie virus (CV) A6, A16 and enterovirus 71) for evidence of the disease. Results: We identified 718 new HFMD patients (161 adults) with peaks in May and August, 2022. Male:female ratio decreased with increasing age. Most children were asymptomatic. A total of 385/409 patients assessed serologically, were found positive, most commonly against CV-A6. Conclusion: Though HFMD typically affects young children, an unusually higher proportion of adults were affected during the current pandemic. There were some differences between pediatric and adult presentation of HFMD.

Distribution and type characteristics of HPV infection of women in Shiyan , Hubei Region / 公共卫生与预防医学

Objective To analyze the distribution and type characteristics of human papillomavirus (HPV) infection in women in Shiyan, Hubei region, so as to provide a basis for the prevention and treatment of HPV infection. Methods From January 2019 to December 2020, a sample of 3,180 women in XX region who had sexual intercourse experience were randomly selected, and their HPV genotypes were tested using flow-through hybridization, then the distribution characteristics and types of HPV infection in women of different ages were observed. Results Among of 3 180 patients, HPV infection was predominant in women aged 31-50 years , with 25.85% (822/3 180) aged 31-40 years and 22.08% (702/3,180) aged 41-50 years. HPV infection was the least prevalent in the ≤25 and >60 years age groups, with 428 cases and 289 cases respectively. HPV infection occurred in 1 310 out of 3 180 women , with a positive infection rate of 41.19% (1 310/3 180). HPV infection was most prevalent in the ≤25 years and ≥60 years age groups, accounting for 56.78% and 67.13% respectively. Single infection was the main infection type in all age groups, accounting for 76.03%. Twenty-one HPV genetic subtypes were detected in the subjects, out of a total of 1 918 strains of the virus. The main high-risk subtypes for single infection were HPV16, HPV52 and HPV58, accounting for 13.92%, 13.87% and 12.57% respectively, followed by HPV53 and HPV33, accounting for 7.61% and 5.58% respectively. The predominant low-risk subtypes for single infection were HPV11, HPV8 and HPV6, with accounting for 7.51%, 5.47% and 5.01% respectively. Conclusion HPV infection in women in Shiyan, Hubei region is predominantly in the ≤25 and ≥60 years age groups, and early clinical screening and preventive measures such as vaccination for high-risk HPV typing are of vital importance.

Genotipificación del virus de la enfermedad mano-pie-boca atípica en un hospital pediátrico de la Ciudad de Buenos Aires, Argentina / Atypical hand-foot-mouth disease virus genotyping in a pediatric hospital in Buenos Aires city, Argentin

La enfermedad mano-pie-boca (EMPB) típica es exantemática, con sintomatología clásica de fiebre, exantema papulovesicular en las manos y los pies, asociada o no a herpangina. Es causada, principalmente, por enterovirus 71 y virus Coxsackie A16, miembros del género Enterovirus. En los últimos años, se han descrito brotes mundiales de EMPB con manifestaciones atípicas causadas, sobre todo, por el virus Coxsackie A6. La EMPB atípica se considera emergente con características clínicas y epidemiológicas peculiares: la afección de adultos, el predominio en invierno y un amplio espectro de manifestaciones clínicas en la extensión y la distribución de las lesiones. Las características morfológicas de las lesiones son muy variables: pueden simular varicela, impétigo o vasculitis.Se describe el caso de un niño de 4 años con EMPB atípica. Se detalla su forma de presentación, evolución clínica, metodología diagnóstica y terapéutica empleada.

Typical hand-foot-mouth disease (HFMD) is an exanthematous viral disease with a classic symptomatology of fever, papulovesicular rash on the hands and feet with or without herpangina. It is usually caused by enterovirus 71 and Coxsackievirus A16, members of the genus Enterovirus. Recently, worldwide outbreaks of HFMD with atypical manifestations caused by Coxsackievirus A6 have been described. Atypical HFMD is considered an emerging disease due to its peculiar clinical and epidemiological characteristics: it affects adults, has a wide spectrum of clinical manifestations in the extension and distribution of the lesions and occurs in winter. The morphological characteristics of the lesions are very variable and can be misdiagnosed as chickenpox, impetigo or vasculitis. Here we describe the symptoms, clinical evolution, diagnostic methodology and treatment employed on a 4-year-old male patient with atypical HFMD.

Estabishment and evaluation of a new method for rapid detection of CA16 hand, foot and mouth disease pathogens based on fluorescence resonance energy transfer technique / 吉林大学学报(医学版)

Objective: To establish a new method for rapid detection of Coxsachie virus A16 (CA16) hand, foot and mouth disease pathogens based on fluorescence resonance energy transfer (FRET) technique, to evaluate the detection effect and to make the method to meet the requirements of large sample size detection during the outbreak of disease. Methods: Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis and bicinchoninic acid (BCA) protein assay were used to identify the purity of CA16 chicken yolk antibody (CA16-IgY) and the protein level. Indirect enzyme-linked immunosorbent assay (iELISA) was used to detect the titer and specificity of anti-CA16 IgY antibody. The size, morphology and characterization of gold nanoparticles (AuNPs) and their biological probes (IgY-AuNPs) were determined by UV-visible spectroscopy (UV-Vis), infrared spectroscopy (FTIR) and transmission electron microscopy (TEM). The CA16 detection system was constructed based on FRET technique. The sensitivity and specificity of the detection method and clinical sample detection were evaluated by optimizing the IgY-AuNPs concentration, sodium chloride (NaCl) dosage, fluorescence recovery time and other indicators. Results: The CA16-IgY had high purity, the titer was 1:128 000, the average protein level was 12. 15 mg · L-1, and CA16-IgY had good specificity. The results of UV-Vis, FTIR and TEM of AuNPs and IgY-AuNPs showed that IgY was successfully labeled onto the surface of AuNPs, which suggested that IgY-AuNPs could specially recognize CA16 was successfully prepared by electrostatic self-assembly. The CA16 detection system was constructed based on FRET technology, after optimization of the detection system, the optimal dosage of IgY-AuNPs was determined to be 0.52 X 10-3 g · L-1, the optimal dosage of NaCl was 40 μL and the optimal fluorescence recovery time was 90 min. The standard curve of the established detection method was I525 ntu= 15. 452 IgC-9. 746, R2 = 0.993 2, the detection limit was as 1 X 104 PFU · ml-1. Compared with qRT-PCR, the agreement rate reached 93. 75%. Conclusion: A new rapid detection method for CA16 hand, foot and mouth disease pathogens is successfully established, which can be applied to laboratory and clinical tests.

Correlation between the levels of plasma brain natriuretic peptide and coxsackie virus A6 in hand, foot and mouth disease / 中国小儿急救医学

Objective@#To investigate the clinical value of plasma brain natriuretic peptide (BNP) levels in predicting the severity of hand, foot and mouth disease (HFMD) in children with coxsackie virus A6 (CV-A6) infection.@*Methods@#A total of 305 children with CV-A6 type HFMD admitted to Xi′an Children′s Hospital from January 2017 to December 2018 were divided into general group (200 cases) and severe group (105 cases) according to the severity of the disease.The receiver operating characteristic curve was used to calculate the value of plasma BNP levels to predict the severe CV-A6 HFMD.Multivariate logistic regression analysis was used to analyze the correlation between the related factors and the severity of CV-A6 HFMD.@*Results@#Compared with the normal group, children in the severe group had statistically significant differences in WBC level, BNP level, neurological symptoms, circulatory disorders, and blood glucose levels(all P<0.05). The optimal cut-off value of the receiver operating characteristic curve for BNP level to predict severe HFMD was 294.85 ng/L.Multivariate logistic regression analysis found that WBC>15×109/L, blood glucose> 8.3 mmol/L, and BNP>294.85 ng/L were related to the severity of CV-A6 HFMD(OR=2.275, P=0.013; OR=6.057, P=0.028; OR=1.008, P<0.001).@*Conclusion@#BNP>294.85 ng/L is closely related to the severity of CV-A6 HFMD and has predictive value.It is an early warning factor for the severity of CV-A6 HFMD.

Enfermedad de mano-pie-boca atípica causada por virus Coxsackie A6 en Argentina, 2015 / Atypical hand, foot, and mouth disease caused by Coxsackievirus A6 in Argentina in 2015

We present two groups of cases of atypical hand, foot, and mouth disease (HFMD) caused by Coxsackievirus A6 (CV-A6) detected in Argentina in 2015. The first group involved 14 patients from Chubut province and the second group affected 12 patients from San Luis province. Molecular analysis of the complete VP1 protein gene revealed the circulation of E2 sublineage, the most predominant worldwide. To our knowledge, this is the first report of CV-A6 infections associated with atypical HFMD in Argentina and South America.

Se describen dos grupos de casos de enfermedad de mano-pie-boca (HFMD) atípica causada por el virus Coxsackie A6 (Coxsackievirus A6, CV-A6) detectados en Argentina en el año 2015. El primero de los grupos involucró a 14 pacientes de Chubut y el segundo a 12 pacientes de San Luis. El análisis molecular del gen de la proteína VP1 completa reveló la circulación del sublinaje E2, el predominante a nivel global. Hasta donde sabemos, este es el primer reporte de infecciones CV-A6 asociadas con HFMD atípica en Argentina y Sudamérica.

Enfermedad de boca, mano, pie en un lactante / Hand, foot, and mouth disease in an infant

Se presenta el caso clínico de un lactante de 9 meses de edad, atendido en el cuerpo de guardia del Policlínico Docente José Martí de la provincia de Santiago de Cuba, por presentar lesiones exantemáticas y eritematosas en la piel, con ampollas alrededor de la boca, así como en manos, piernas y ambos pies, además de fiebre. Se le diagnosticó la enfermedad de boca, mano y pie, teniendo en cuenta la clínica y el incremento de esta afección trasmitida por el virus de Coxsackie en el municipio, por lo cual fue ingresado en el hogar, con vigilancia y seguimiento por su médico y enfermera de la familia, quienes indicaron las medidas para el control higiénico sanitario y de sostén que deben conocerse y aplicarse en el medio familiar para disminuir el riesgo de la infección.

The case report of a 9 months of age infant assisted in the emergency room of José Martí Teaching Polyclinic in Santiago de Cuba is presented, due to exanthematic and erythematous lesions in the skin, with bladders around the mouth, as well as in hands, legs and both feet, besides fever. The mouth, hand and foot disease was diagnosed, keeping in mind the clinic and the increment of this disorder transmitted by the Coxsackie virus in the municipality, reason why he was admitted at home, with medical supervision and followed by the family nurse and physician who indicated the measures for the health control that should be known and applied in the family to decrease the risk of infection.

Animal Models of EV71 and CA16 Hand-foot-mouth Disease and Characteristics of Viral Infection / 中国实验方剂学杂志

Hand-foot-mouth disease (HFMD) is a common infectious disease caused by enterovirus in children. It has a high incidence and can cause fatal complications such as pulmonary edema, myocarditis and aseptic meningitis, seriously threatening the health of children. At present, some core problems such as the pathogenesis of disease, the relationship between different genotypes of pathogenic viruses, the pharmacodynamic evaluation methods, and the antiviral mechanism of drugs are still unclear. The construction of disease animal models with simulation performance of human exposure is the key to solve the above problems. Researchers both at home and abroad have established a variety of animal models for HFMD, of which enterovirus 71 (EV71) and coxsackievirus A16 (CA16) are most common and most widely used. Both EV71 and CA16 are enterovirus A in picornavirus family, so they have similarities in terms of pathogenicity, infection and replication characteristics, clinical symptoms caused by infection and immune response, but also have significant differences in age of susceptibility, method of infection, as well as neurotoxicity, clinical symptoms and signs, and degree of tissue and organ damage. Therefore, researchers shall select and establish proper animal models based on actual conditions, which is critical to the reliability of the results. In this paper, the different types of HFMD animal models established by EV71 and CA16 viruses were reviewed, especially on the species strains, virus strain types, infection methods, and characteristics of viral infections in each model, and the characteristics and clinical symptoms of HFMD induced by EV71 and CA16 were also investigated to provide reference for related research.

The clinical manifestations and treatment of hand, foot and mouth disease caused by Coxsackievirus A6 / 中国小儿急救医学

Hand-foot-and-mouth disease (HFMD) is a common infectious disease caused by human enterovirus (EVs). It is more common in children under 5 years of age.The clinical symptoms are mainly rash and herpes in the hands, feet, mouth and other parts.Some serious cases may suffer from serious complications in nervous system, respiratory system or circulatory system.Since 1998, HFMD has been mainly caused by enterovirus 71 and coxsackievirus A16 (CV-A16). In the past 10 years, coxsackievirus A6(CV-A6) has gradually replaced EV-71 and CV-A16, and become a main pathogen of HFMD.Many literatures have shown that CV-A6 often causes atypical HFMD, which is mainly characterized by a wider and more serious rash and desquamation, and even onychomadesis.At present, there are some reports on the prevalence and detection methods of HFMD caused by CV-A6.The paper reviewed on CV-A6 related etiology, epidemiology, clinical manifestations and treatment of HFMD.

Expression of the VP1 protein and establishment of indirect ELISA detection method of Coxsackievirus B4 / 中华实验和临床病毒学杂志

Objective@#To detect antibodies to Coxsackievirus B4 (CV-B4), the indirect enzyme-linked immunosorbent assay (ELISA) method was established and optimized using the recombinant VP1 protein expressed in the prokaryote system as the envelope antigen.@*Methods@#The VP1 gene of CV-B4 was amplified using reverse transcriptase-polymerase chain reaction (RT-PCR). It was ligated into the expression vector pET32a(+ ) to obtain the recombinant plasmid pET32(+ )-VP1 and was then transformed into E. coli expression strain Rosetta (DE3). The recombinant VP1 protein was induced by IPTG, which was verified using SDS-PAGE electrophoresis and mass spectrometry. The establishment and optimization of the indirect ELISA reaction system was based on the purified recombinant protein mentioned above as the coating antigen.@*Results@#The CV-B4 VP1 gene was stably expressed in E. coli in the form of inclusion body. The optimal coating concentration of antigen was 7.5 μg per well and the optimal serum dilution was 1∶100. The threshold for determining the negative and positive result of the serum samples was the optical density value of ≥ 0.376 at 450 nm. The purified recombinant protein could be specifically recognized by CV-B4 positive serum without cross-reaction with Coxsackievirus (CV)-A, CV-B1 and CV-B5, indicating that it has good immunogenicity. However, it can cross-react with CV-B3 serum samples.@*Conclusions@#The indirect ELISA detection method based on the CV-B4 VP1 protein could be used in the detection of serum antibody to CV-B4 infection with good sensitivity, specificity and repeatability.

Effects of particulates in four different air pollution sources and coxsackie virus B3 on autophagy and apoptosis of cardiac myocytes in rats / 中华实验和临床病毒学杂志

Objective@#To observe the changes of LC3, lc3-Ⅱ/lc3-Ⅰ ratio, Nrf2 and Bcl2 in myocarditis induced by coxsackievirus group B type 3 (CV-B3) infection and myocardial damage in SD rats caused by particulate matter of four different pollution sources, and to further explore the mechanism of autophagy and apoptosis of myocardial cells and myocardial damage.@*Methods@#Adult SD rats were randomly divided into CV-B3 infection group (20 rats), automobile exhaust group (20 rats), coal smoke group (20 rats), burning straw group (20 rats), atmosphere group (20 rats) and control group (20 rats). The expressions of LC3, Bcl2 and Nrf2 in rats were detected by Western blot at 12 hours, 48 hours, 5 days and 10 days.@*Results@#In the first three groups of rats expression of LC3, Bcl2 and Nrf2 was upregulated, this was seen early in CV-B3 group, the peak was high, and recovery was fast; while in automobile exhaust group the above changes appeared later, the amplitude was low; in the coal smoke group rats the above changes appeared even later, but the amplitude of change was higher than that in automobile exhaust group, but lower than that of CV-B3 group. In automobile exhaust and coal smoke groups Bcl2 and Nrf2 expression was still slightly increased at day 10. After 48 hours, the above measurements in rats in the atmosphere group were temporarily up-regulated, and returned to normal on day 5. The above measurements of rats in the straw smoke and the control group did not show significant change.@*Conclusions@#In the SD rats with acute viral myocarditis induced by CV-B3 and myocardial damage induced by automobile exhaust, coal smoke and atmospheric particulate matter, the whole process of metabolism, renewal, repair and anti-damage activity of myocardial cells can be accomplished through autophagy activation, apoptosis inhibition and antioxidant mechanism.

Role of autophagy in the pathogenesis of myocarditis / 国际儿科学杂志

Myocarditis refers to diffuse or focal inflammatory cell infiltration of the myocardial interstitium and necrosis or degeneration of adjacent myocardial fiber caused by infection or other causes,which is one of the common diseases that cause the death of infants and adolescents.Viral infection is the main pathogenic factor,but the pathogenesis of myocarditis has not yet been fully elucidated.Autophagy is a highly conservative process of self-digestion,which can provide amino acids,ATP and other substances for cells in the state of inflammation or starvation to help cells survive the energy crisis under excessive stimulation.However,excessive autophagy can promote the replication of viruses,which leads to autophagic death.In recent years,some researchers found that autophagy is closely related to the process of viral myocarditis associated with Coxsackie virus B3.The role of autophagy in the pathogenesis of myocarditis is reviewed in this article.

Eccema coxsackium en adulto: presentación de un caso / Eczema coxsackium in adults: a case report

La enfermedad de pie, mano boca es una patología frecuente de observar en niños menores de 5 años, generalmente producida por virus Coxsackies y Enterovirus. Existen presentaciones atípicas debido a serotipos recientemente descritos de estos virus, algunos de ellos se han reportado en pacientes adultos. Se presenta caso de paciente masculino de 19 años, con antecedentes de dermatitis seborreica facial en tratamiento, que desarrolla una presentación atípica del síndrome pie, mano boca en contexto de un brote de esta patología en su academia militar. Luego del análisis epidemiológico, clínico e histopatológico, se diagnostica eccema coxsackium, una patología infrecuente en este grupo etario que contiene algunas particularidades destacables en relación con su manejo y estudio.

The hand mouth foot syndrome is a common pathology observed in children under 5 years, usually caused by coxsackie virus and enterovirus. There are exuberant clinical presentations, due to infrequent and emerging serotypes of these viruses, some of them manifesting in adult patients. A case of a 19 year old patient is presented, with a history of seborrheic dermatitis of the face and scalp in treatment, who develops an atypical clinical presentation of the hand foot mouth syndrome, intensely affecting the areas of seborrheic dermatitis on the face, in the context of an outbreak of this pathology in his military academy. After the epidemiological, clinical and histopathological analysis, eczema coxsackium is diagnosed, an infrequent pathology in this age group that contains some remarkable peculiarities in relation to its management.

Onicomadesis asociada a la enfermedad de boca, mano, pie / Onychomadesis associated to mouth, hand, and foot disease

Introducción: la onicomadesis es el desprendimiento completo y espontáneo de la uña desde su extremo proximal, sin dolor o inflamación, consecutivo a la detención mitótica de la matriz ungular que conlleva a un cambio de su función. Objetivo: describir una serie de casos de onicomadesis atendidos en la consulta de Dermatología del Hospital Pediátrico Docente del Cerro, entre noviembre y diciembre del año 2017, después de presentar un cuadro clínico compatible con enfermedad boca, mano, pie, con la finalidad de contribuir al conocimiento de esta patema. Presentación de los casos: las edades estuvieron comprendidas en un rango entre 1 y 12 años, con solo 3 pacientes correspondientes al sexo masculino y solo uno con el color de la piel negra. Los días previos al padecimiento de la enfermedad boca, mano, pie se enmarcan entre 15 y 47 días de haber tenido los síntomas que indujeron al diagnóstico del citado morbo. El estudio virológico se efectuó en dos pacientes con presencia del Coxsackie A6. La evolución resultó satisfactoria en todos los casos. Conclusiones: los hallazgos, en general, coinciden con los mencionados en la literatura. Todos los pacientes presentaron semanas anteriores signos y síntomas compatibles con enfermedad boca, mano, pie. Es necesario orientar a los padres de los enfermos con este morbo, la posibilidad de la ocurrencia de onicomadesis como complicación, cuyo tratamiento es sintomático, seguido de buen pronóstico, para evitar la ansiedad familiar y los gastos de recursos innecesarios(AU)

Introduction: onychomadesis is the total and spontaneous detachment of the nail from its proximal end, without pain or inflammation, and following the mitotic halting of the nail matrix that leads to a change in its function. Objective: to describe a series of cases of onychomadesis attended in the Dermatology clinic of the Pediatric Teaching Hospital of Cerro, in the period of November to December of 2017, after presenting clinical manifestations compatible with mouth, hand, and foot disease, and in order to contribute to the knowledge of this pathology. Presentation of cases: ages were among 1 and 12 years old, with only 3 patients corresponding to the male sex and only one with black skin. The days before presenting symptoms of mouth, hand, and foot disease were between 15 and 47 days after having the symptoms that led to the diagnosis of the aforementioned disease. The virological study was carried out in two patients with the presence of Coxsackie A6. The evolution was satisfactory in all cases. Conclusions: in general the findings coincide with those mentioned in the literature. All patients presented previous signs and symptoms compatible with mouth, hand, and foot disease in the previous weeks. It is necessary to guide the parents of patients with this disease on the possibility of the onychomadesis occurrence as a complication, whose treatment is symptomatic, followed by a good prognosis to avoid family anxiety and the expense of unnecessary resources(AU)

Características clínico epidemiológicas de pacientes pediátricos con enfermedad boca, mano, pie / Clinical epidemiological characteristics of pediatric patients with mouth, hand and foot disease

Introducción: la enfermedad boca, mano, pie es una enfermedad febril eruptiva provocada por la infección por los virus Coxsackie, consistente en fiebre, exantema pápulo-vesicular en las manos, los pies y un enantema ulceroso en la boca. Objetivos: indagar la etiología viral y describir las características clínico epidemiológicas de la entidad. Métodos: estudio descriptivo prospectivo en 54 pacientes menores de 18 años, diagnosticados con la enfermedad boca, mano, pie, atendidos en el Hospital Pediátrico Docente del Cerro, de septiembre a noviembre de 2017. Se incluyeron aquellos con lesiones vesiculares o pápulas vesiculares, distribuidas en la piel y úlceras en la mucosa oral; y se excluyeron los pacientes con otras entidades exantemáticas o vesiculares. Las variables investigadas resultaron: la edad, el sexo, los signos, los síntomas clínicos de infección, el leucograma y el estudio virológico. La selección de la muestra fue de manera no probabilística consecutiva. Los datos se procesaron por el paquete estadístico XLSTAT con análisis univariado. Resultados: el grupo entre 1-3 años obtuvo 53,7 por ciento, y el sexo masculino el 68,5 por ciento. Las lesiones cutáneas fueron más frecuentes en la cara, las extremidades, los glúteos y el tronco (68,6 por ciento), seguido de la zonas de la cara, las extremidades y el tronco (29,6 por ciento). El enantema fue apreciado en el 48,1 por ciento, la fiebre en el 61,1 por ciento, la fiebre más secreción nasal en el 44,4 por ciento y el prurito en el 70,3 por ciento. El conteo leucocitario alcanzó 11,1 x 109 células. Los polimorfonucleares obtuvieron promedio de 37,9 y los linfocitos 70,3. En 49 de los 54 pacientes se aisló el virus Coxsackie A6. Conclusiones: se describe la enfermedad boca, mano, pie en forma atípica, cuyo cuadro clínico coincide con lo aparecido en la literatura(AU)

Introduction: mouth, hand and foot disease is an eruptive febrile illness caused by the infection of Coxsackie viruses, and it consists in fever, papulo-vesicular exanthema in the hands, feet and an ulcer enanthema in the mouth. Objectives: to investigate the viral etiology and describe the clinical epidemiological characteristics of the entity. Methods: prospective descriptive study in 54 patients under 18 years old diagnosed with mouth, hand and foot disease, and whom were attended at the Pediatric Teaching Hospital of Cerro from September to November 2017. Those with vesicular lesions or vesicular papules distributed in the skin, and ulcers in the oral mucosa were included in the research; and patients with other exanthematic or vesicular entities were excluded. The variables investigated were: age, sex, signs, clinical symptoms of infection, leukogram and virological study. The selection of the sample was consecutive non-probabilistic. The data was processed by the XLSTAT statistical package with univariate analysis. Results: the group from 1 to 3 years old represented the 53.7 percent, and the male sex the 68.5 percent y. Skin lesions were more frequent on the face, extremities, buttocks and trunk (68.6 percent), followed by facial, limbs and trunk areas (29.6 percent). Enanthem was visible in 48.1 percent, and fever appeared in 61.1 percent, fever plus nasal discharge in 44.4 percent and itching in 70.3 percent y The leukocyte count reached 11.1 x 109 cells. Polymorphonuclear cells obtained an average of 37.9 and lymphocytes of 70.3. In 49 of the 54 patients the Coxsackie A6 virus was isolated. Conclusions: mouth, hand, and foot disease is described in an atypical form, whose clinical manifestations coincide with what appeared in the literature(AU)

Epidemiological characteristics of Coxsackie virus A16 caused hand foot and mouth disease cases in Guangdong province, 2012-2016 / 中华流行病学杂志

Objective To analyze the epidemiological characteristics of hand foot and mouth disease (HFMD) cases caused by Coxsackie virus A16 (Cox A16) in Guangdong province from 2012 to 2016.Methods The data of mild HFMD cases caused by Cox A 16 were collected from 8 sentinel hospitals in 8 prefecture-level cities in Guangdong to estimate Cox A16 infection status and its population and time distribution characteristics.Results (1) The highest estimated incidence of Cox A16 infection was in 2014 (113.0/100 000),followed by 2016 (86.4/100 000) and 2012 (79.1/100 000),while the estimated incidence was lower in 2015 (29.0/100 000) and 2013 (28.8/100 000).(2) Cox A16 was confirmed to be the predominant pathogen causing HFMD outbreaks (54.6％,89/163).The number of outbreaks in the year with high incidence (28 outbreaks) was 11.2 times higher than that in the year with low incidence (2.5 outbreaks).(3) Across all age groups,the annual estimated incidence of Cox A16 infection decreased with age (trend x2=853 905.63,P＜0.01).The incidence was highest in age group 1 year (1 449.2/100 000),followed by that in age group 3 years (1 097.0/100 000),in age group 2 years (1 083.5/100 000),in age group 4 years (687.8/100 000) and in age group 0 year (604.9/100 000).Among the age groups ＜12 months,the estimated incidence increased with age (trend g2=5 541.77,P ＜ 0.01),which was highest in age group 11-months (2 105.1/100 000),followed by that in age groups 10-months (1 448.6/100 000),9-months (938.3/100 000),8-months (703.3/100 000) and 6-months (664.6/100 000).(4) The annual incidence peak was during May (143.9/100 000)-June (131.5/100 000).Conclusion The prevalence of Cox A16 infection differed with year in Guangdong during 2012-2016.When the incidence of Cox A16 infection was high,more outbreaks occurred.The prevalence occurred mainly in nurseries and kindergartens from May to June each year.Children aged 0-4 years were the high risk group for Cox A16 infection,children aged 6-11 months were at high risk for Cox A16 infection.

Epidemiological characteristics of Coxsackie virus A16 caused hand foot and mouth disease cases in Guangdong province, 2012-2016 / 中华流行病学杂志

Objective To analyze the epidemiological characteristics of hand foot and mouth disease (HFMD) cases caused by Coxsackie virus A16 (Cox A16) in Guangdong province from 2012 to 2016.Methods The data of mild HFMD cases caused by Cox A 16 were collected from 8 sentinel hospitals in 8 prefecture-level cities in Guangdong to estimate Cox A16 infection status and its population and time distribution characteristics.Results (1) The highest estimated incidence of Cox A16 infection was in 2014 (113.0/100 000),followed by 2016 (86.4/100 000) and 2012 (79.1/100 000),while the estimated incidence was lower in 2015 (29.0/100 000) and 2013 (28.8/100 000).(2) Cox A16 was confirmed to be the predominant pathogen causing HFMD outbreaks (54.6％,89/163).The number of outbreaks in the year with high incidence (28 outbreaks) was 11.2 times higher than that in the year with low incidence (2.5 outbreaks).(3) Across all age groups,the annual estimated incidence of Cox A16 infection decreased with age (trend x2=853 905.63,P＜0.01).The incidence was highest in age group 1 year (1 449.2/100 000),followed by that in age group 3 years (1 097.0/100 000),in age group 2 years (1 083.5/100 000),in age group 4 years (687.8/100 000) and in age group 0 year (604.9/100 000).Among the age groups ＜12 months,the estimated incidence increased with age (trend g2=5 541.77,P ＜ 0.01),which was highest in age group 11-months (2 105.1/100 000),followed by that in age groups 10-months (1 448.6/100 000),9-months (938.3/100 000),8-months (703.3/100 000) and 6-months (664.6/100 000).(4) The annual incidence peak was during May (143.9/100 000)-June (131.5/100 000).Conclusion The prevalence of Cox A16 infection differed with year in Guangdong during 2012-2016.When the incidence of Cox A16 infection was high,more outbreaks occurred.The prevalence occurred mainly in nurseries and kindergartens from May to June each year.Children aged 0-4 years were the high risk group for Cox A16 infection,children aged 6-11 months were at high risk for Cox A16 infection.

Prokaryotic expression of coxsackie virus A6 genes and preparation of polyclonal antibody against the VP1 and VP2 protein / 中华实验和临床病毒学杂志

Objective@#To construct the prokaryotic plasmid expressing the recombinant protein Coxsackie virus A6 VP1 or VP2 and prepare the antiserum of rabbit anti-CVA6 VP1 or anti-CVA6 VP2.@*Methods@#CVA6 VP1and VP2 gene fragments were amplified by reverse transcription PCR and inserted into the prokaryotic expression vectors. The recombinant plasmids were expressed in E. coli BL21 (DE3). After induction with Isopropyl β-D-Thiogalactoside (IPTG), the fusion proteins were obtained, and then purified by SDS-PAGE electrophoresis and gel extraction. The polyclonal antibodies were prepared by immunizing rabbits with the fusion proteins and analyzed with Western blot(WB) and indirect immunofluorescence assay(IFA).@*Results@#The prokaryotic expression vector of CVA6 VP1 or VP2 was confirmed by PCR, double enzyme digestion and sequencing. CVA6 VP1 and VP2 fusion proteins with high purity were obtained. WB and IFA were used to identify polyclonal antibodies.@*Conclusions@#The CVA6 VP1 and VP2 prokaryotic expression vectors were successfully constructed, and the recombinant CVA6 VP1 and VP2 proteins and their corresponding polyclonal antibodies were obtained.

Suspected pathogen detection and epidemiological analysis of hand, foot and mouth disease in Minhang District of Shanghai from 2009 to 2016 / 复旦学报（医学版）

Objective To investigate the etiological agents of the outbreak of hand,foot and mouth disease (HFMD) in Minhang District of Shanghai from 2009 to 2016,and to provide evidence for the prevention and management policy of HFMD by collecting suspected HFMD samples for laboratory testing from HFMD sentinel hospitals,the Children's Hospitals of Fudan University and jurisdiction community health service centers.Methods Specimens including stools,throat swabs and anal swabs were collected from patients suspected of HFMD from surveillance hospitals,i.e.,Children's Hospital of Fudan University and jurisdiction community health service centers during 2009 and 2016.The specimens were detected by real-time RT-PCR with the five types of viruses including panenterovirus (EV),enterovirus 71 (EV71),Coxsackie virus A16 (CVA16),Coxsackie virus A6 (CVA6) and Coxsackie virus A10 (CVA10).The distribution characteristics of pathogens were analyzed.Results During 2009 and 2016 we collected 3 744 cases of HFMD,the positive detection rate of pan-enterovirus were 84.83％ (3 176 cases),including EV71 (64.45％) and CVA16 (15.77％),then were CVA6 (9.23％) and other EV (8.78％),and CVA10 was only 0.76％.The major etiological agent was EV71.The advantage of different years and different season strain presented dynamic change,mainly EV71 and CVA16 co-popular in 2009,mainly EV71 epidemic from 2010 to 2011,EV71 and CVA16 were co-popular again in 2012,and the priority was EV71,then EV71 and other EV were co-popular in 2013.After 2014,CVA6 gradually increased,mainly CVA6 was popular 2015 and 2016,especially in 2016,the proportion of CVA6 ranged as high as 40.55％.CVA10 showed sporadic distribution trend in very low proportion.From the difference of age and gender in HFMD cases,the males were more than the females (1.68 ∶ 1),and the incidence was the highest in children of 1-3 years old.The peak of incidence occured in April to July,then in September to November.Conclusions HFMD onset seasons mainly were summer and fall-and-winter in bimodal popular models.It happens in children under 5 years of age.The incidence was higher in male than in female.The advantage of different years and different season strains present dynamic change,and the prevalence has obvious age and season limit.

Suspected pathogen detection and epidemiological analysis of hand, foot and mouth disease in Minhang District of Shanghai from 2009 to 2016 / 复旦学报（医学版）

Objective To investigate the etiological agents of the outbreak of hand,foot and mouth disease (HFMD) in Minhang District of Shanghai from 2009 to 2016,and to provide evidence for the prevention and management policy of HFMD by collecting suspected HFMD samples for laboratory testing from HFMD sentinel hospitals,the Children's Hospitals of Fudan University and jurisdiction community health service centers.Methods Specimens including stools,throat swabs and anal swabs were collected from patients suspected of HFMD from surveillance hospitals,i.e.,Children's Hospital of Fudan University and jurisdiction community health service centers during 2009 and 2016.The specimens were detected by real-time RT-PCR with the five types of viruses including panenterovirus (EV),enterovirus 71 (EV71),Coxsackie virus A16 (CVA16),Coxsackie virus A6 (CVA6) and Coxsackie virus A10 (CVA10).The distribution characteristics of pathogens were analyzed.Results During 2009 and 2016 we collected 3 744 cases of HFMD,the positive detection rate of pan-enterovirus were 84.83％ (3 176 cases),including EV71 (64.45％) and CVA16 (15.77％),then were CVA6 (9.23％) and other EV (8.78％),and CVA10 was only 0.76％.The major etiological agent was EV71.The advantage of different years and different season strain presented dynamic change,mainly EV71 and CVA16 co-popular in 2009,mainly EV71 epidemic from 2010 to 2011,EV71 and CVA16 were co-popular again in 2012,and the priority was EV71,then EV71 and other EV were co-popular in 2013.After 2014,CVA6 gradually increased,mainly CVA6 was popular 2015 and 2016,especially in 2016,the proportion of CVA6 ranged as high as 40.55％.CVA10 showed sporadic distribution trend in very low proportion.From the difference of age and gender in HFMD cases,the males were more than the females (1.68 ∶ 1),and the incidence was the highest in children of 1-3 years old.The peak of incidence occured in April to July,then in September to November.Conclusions HFMD onset seasons mainly were summer and fall-and-winter in bimodal popular models.It happens in children under 5 years of age.The incidence was higher in male than in female.The advantage of different years and different season strains present dynamic change,and the prevalence has obvious age and season limit.